Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

• Main Authors: Peng J, Zhao K, Zhu J, Wang Y, Sun P, Yang Q, Zhang T, Han W, Hu W, Yang W, Ruan J, Qian Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-08-01
• Series: Drug Design, Development and Therapy
• Subjects: sarsasapogenin; osteoclast; osteoclastogenesis; nf-κb; mapk; nfatc1; therapeutics
• Online Access: https://www.dovepress.com/sarsasapogenin-suppresses-rankl-induced-osteoclastogenesis-in-vitro-an-peer-reviewed-article-DDDT

Jiaxuan Peng,1,* Kangxian Zhao,2,* Jiling Zhu,3,* Yanben Wang,4,5 Peng Sun,2 Qichang Yang,2 Tan Zhang,4 Weiqi Han,4 Wenjun Hu,4 Wanlei Yang,4 Jianwei Ruan,6 Yu Qian1,2,4 1Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, People’s Republic of China; 2The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 3Department of Clinical Medicine, Medical College of Shaoxing University, Shaoxing, Zhejiang 312000, People’s Republic of China; 4Department of Orthopaedics, Shaoxing People’s Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang, People’s Republic of China; 5Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopaedics, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang, Republic of China*These authors contributed equally to this workCorrespondence: Yu QianDepartment of Orthopaedics, Shaoxing People’s Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang, People’s Republic of ChinaEmail [e-mail]: Osteoclasts are giant polynuclear cells; their main function is bone resorption. An increased number of osteoclasts and enhanced bone resorption exert significant effects on osteoclast-related bone-lytic diseases, including osteoporosis. Given the limitations of current therapies for osteolytic diseases, it is urgently required to develop safer and more effective alternatives. Sarsasapogenin, a major sapogenin from Anemarrhena asphodeloides Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear.Methods: We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts.Results: Sarsasapogenin inhibited multiple RANKL-induced signaling cascades, thereby inhibiting the induction of key osteoclast transcription factor NFATc1. The in vivo and in vitro results were consistent: sarsasapogenin treatment protected against bone loss in a mouse osteolysis model induced by lipopolysaccharide.Conclusion: Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.Keywords: sarsasapogenin, osteoclast, osteoclastogenesis, NF-κB, MAPK, NFATc1, therapeutics